PolyADP-ribose is a polymer that is associated with the chromatin of eukaryotic cells. It is formed from NAD and has been shown to inhibit the capacity of nuclear DNA to function as a template for DNA polymerase. In neoplastic cells, NAD levels are known to be depressed. Because polyADP-ribose is formed from NAD and is involved in the regulation of DNA replication, the possibility exists that there is a relationship between the low levels of NAD in tumors and their property of continuous proliferation. Intracellular levels of NAD may thus play an important role in the control of cell proliferation. However, little is currently known about the regulation of NAD levels in tissues. The information that is available suggests that intracellular NAD is controlled by the enzyme NAD glycohydrolase, which acts by hydrolyzing excess NAD. In the research that is proposed, the relationships between NAD, polyADP-ribose, polyADP-ribose polymerase, NAD glycohydrolase, and cell proliferation will be explored. Because normal and malignant cells are expected to differ widely with regard to these biochemical parameters, both normal and leukemic human leukocytes will be examined, using microtechniques wherever necessary. In addition to freshly- isolated leukocytes, leukocytes that have been cultured under short-term conditions, and leukocytes that have become established in long-term tissue culture will be studied.